Cervical Cancer Screening With Human Papillomavirus Testing

Short-term repeat HPV testing for triaging HPV-positive women in cervical cancer screening

Persistent HPV infection causes cervical cancer, but most infections are transient. Triage methods identify high-risk women needing further evaluation or treatment. We assessed short-term repeat HPV testing as an alternative triage option. In ESTAMPA, women aged 30-64 years were screened with HPV testing (HC2 or Cobas) and cytology. Screen positives were referred to colposcopy approximately two months after screening, where cervical samples were collected again for repeat HPV testing. We evaluated the performance of repeat HPV for CIN3+ among HPV-positive women and explored its combination with limited HPV genotyping (HPV16/18). Among 5390 HPV-positive women (including 629 CIN3 cases and 53 cancers), 61% retested positive at ~2 months (median: 1.8, interquartile range: 1.2-2.8). Repeat HPV sensitivity for CIN3+ was 81.5% (95% CI 77.2-85.2) for HC2 and 87.7% (83.7-90.8) for Cobas. Specificity was <50% with referral rates of 57.4% (55.7-59.0) and 68.2% (66.1-70.2) for HC2 and Cobas. HPV16/18 genotyping followed by repeat HPV among non-HPV16/18-positive women did not greatly improve performance. However, HPV16/18 positivity doubled the risk of CIN3+, supporting its combination with repeat HPV when available. Short-term repeat HPV testing could be a practical option for triaging HPV-positive women, either alone or in combination with limited HPV genotyping. ClinicalTrials.gov, NCT01881659.

Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen‐positive women: results from the ESTAMPA study

AbstractVIA is recommended for triage of HPV‐positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV‐positive women was evaluated. Women aged 30‐64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study‐trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty‐two HPV‐positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2‐89.5) among women &lt;50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9‐86.6). Overall specificity was 58.6% (95% CI 56.7‐60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8‐73.5) compared to women &lt;50 (54.3%, 95% CI 52.1‐56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9‐38.6) compared to women &lt;50 (53.2, 95% CI 51.1‐55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%‐95.4%, 44.9%‐94.4%, 8.2%‐65.3%, 0%‐98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV‐positive women performed by trained providers was high with an important reduction in referral rates. However, scaling‐up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol

Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659

Armando Baena

Maribel Almonte